Final Research Plan

Iron Deficiency and Iron Deficiency Anemia During Pregnancy: Screening and Supplementation

July 07, 2022

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The analytic framework depicts the relationship between the population, intervention, outcomes, and harms of supplementation for the prevention of iron deficiency and iron deficiency anemia during pregnancy. The far left of the framework describes the target population as pregnant persons asymptomatic for iron deficiency and iron deficiency anemia. To the right of the population is an arrow which leads to the intervention routine iron supplementation. Below routine iron supplementation is an oval for harms of screening (Key Question 2). An arrow leads directly from the intervention to a box containing health outcomes maternal and infant morbidity and mortality, including birth outcomes, and quality of life (Key Question 1). An arrow to the right of the intervention leads to a rounded edge box containing the intermediate outcome of iron status. A dotted line to the right of iron status represents the connection between iron status and health outcomes maternal and infant morbidity and mortality, including birth outcomes, and quality of life (Key Question 3).

Abbreviation: KQ=key question.

The analytic framework depicts the populations, interventions, outcomes, and harms of interest for screening for iron deficiency and iron deficiency anemia in pregnant persons. The far left of the framework describes the target population as pregnant persons asymptomatic for iron deficiency and iron deficiency anemia. To the right is screening. An arrow leads directly from screening to a box containing the health outcomes maternal and infant morbidity and mortality, including birth outcomes, and quality of life (Key Question 1). Below screening is an oval for harms of screening (Key Question 2). To the right of screening is a box for iron deficiency. An arrow to the right of iron deficiency represents the intervention iron treatment and leads to the intermediate outcome of iron status (Key Question 3). Below the intervention is an oval for harms of iron treatment (Key Question 4). A dotted line to the right of iron status represents the connection between iron status and health outcomes maternal and infant morbidity and mortality, including birth outcomes, and quality of life (Key Question 5).

Abbreviation: KQ=key question.

  1. What are the benefits of routine iron supplementation during pregnancy on maternal and infant health outcomes?
  2. What are the harms of routine iron supplementation during pregnancy?
  3. In pregnant persons with iron deficiency, with or without anemia, what is the association between change in maternal iron status (including changes in ferritin or hemoglobin level) and improvement in newborn and peripartum outcomes in U.S.-relevant populations?
  1. What are the benefits of screening for iron deficiency and iron deficiency anemia during pregnancy on maternal and infant health outcomes?
  2. What are the harms of screening for iron deficiency and iron deficiency anemia during pregnancy?
  3. What are the benefits of treatment of iron deficiency and iron deficiency anemia during pregnancy on maternal and infant health outcomes?
  4. What are the harms of iron treatment during pregnancy?
  5. In pregnant persons with iron deficiency, with or without anemia, what is the association between change in maternal iron status (including changes in ferritin or hemoglobin level) and improvement in newborn and peripartum outcomes in U.S.-relevant populations?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What are the current practices in identifying pregnant persons with iron deficiency and iron deficiency anemia? Do current practices of identification differ by race or ethnicity, diagnostic criteria, age, socioeconomic status, cultural factors, educational attainment, insurance status, or health literacy of the pregnant person?
  2. What are current practices for the use of iron supplementation during pregnancy? Do current practices differ by race or ethnicity, diagnostic criteria, age, socioeconomic status, cultural factors, educational attainment, insurance status, or health literacy of the pregnant person?
  3. How well do risk assessment tools identify pregnant persons at increased risk for iron deficiency anemia?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions.

Category Included Excluded
Populations Asymptomatic adults (age ≥18 years) and adolescents (ages 13 to <18 years), regardless of iron status, who are pregnant and their infants Nonpregnant persons; persons with underlying diagnosis or symptoms of anemia; and severely malnourished populations not representative of those in the United States
Interventions Oral iron supplementation, iron-fortified foods Nonoral forms of iron
Comparators All KQs: No supplementation

KQ 3: A change in maternal iron deficiency status, iron deficiency anemia status, or both

  
Outcomes KQ 1:

Maternal health outcomes: Mortality; health-related quality of life; preeclampsia (severe); postpartum hemorrhage; blood transfusion; postpartum depression
Maternal intermediate outcomes: Incidence of iron deficiency anemia; incidence of iron deficiency; hematologic indices and ferritin levels; and cesarean delivery rates
Infant health outcomes: Perinatal mortality, respiratory distress, and NICU admission
Infant intermediate outcomes: Hematologic indices and ferritin levels; low birth weight, small for gestational age, and preterm delivery

KQ 2: More serious harms; harms leading to discontinuation; accidental overdose

 Infant outcomes occurring after age 1 year
Settings U.S. primary care–relevant settings  
Timing KQ 1: Long-term outcomes

KQ 2: Short- or long-term outcomes

  
Study Designs KQ 1: Randomized, controlled trials; controlled cohort studies; and other controlled observational studies

KQ 2: Studies from KQ 1 and large uncontrolled observational studies

 KQ 1: Uncontrolled studies

Abbreviations: KQ = key question, NICU = neonatal intensive care unit.

Category Include Exclude
Populations KQs 1, 2: Pregnant adolescents and adults and their infants who are asymptomatic for iron deficiency or iron deficiency anemia

KQs 3, 4: Pregnant adolescents and adults with iron deficiency anemia and their infants

KQ 5: Pregnant persons with iron deficiency, with or without anemia, and their infants

Nonpregnant persons; severely malnourished populations not representative of those in the United States; persons who are symptomatic for iron deficiency or iron deficiency anemia
Interventions

KQs 1, 2: Screening for iron deficiency anemia

KQs 3, 4: Oral or intravenous iron supplementation, iron-fortified foods

 Nonoral and nonintravenous forms of iron
Comparators KQs 1, 2: No screening for iron deficiency anemia

KQs 3, 4: No treatment

KQ 5: A change in maternal iron deficiency status, iron deficiency anemia status, or both		 No comparison
Outcomes KQs 1, 3, 5:

Maternal health outcomes: Mortality; health-related quality of life; preeclampsia (severe); postpartum hemorrhage; blood transfusion; postpartum depression
Maternal intermediate outcomes: Cesarean delivery rates
Infant intermediate outcomes: Hematologic indices and ferritin levels; low birth weight, small for gestational age, and preterm delivery

KQ 2: Overdiagnosis, anxiety, and labeling

KQ 3:

Maternal intermediate outcomes: Incidence of iron deficiency anemia; incidence of iron deficiency; hematologic indices and ferritin levels
Infant health outcomes: Perinatal mortality, morbidity (NICU admission, respiratory distress)

KQ 4: More serious harms; harms leading to discontinuation; overtreatment

 Infant outcomes >1 year of age
Settings U.S. primary care–relevant  
Timing KQs 1, 3: Long-term outcomes

KQs 2, 4, 5: Short- or long-term outcomes

  
Study Designs KQs 1, 3: Randomized, controlled trials; controlled cohort studies; and other controlled observational studies

KQs 2, 4: Studies included from other KQs and large uncontrolled observational studies

KQ 5: Association studies

 Uncontrolled studies (KQs 1 and 3)

Abbreviations: KQ = key question; NICU = neonatal intensive care unit.

The draft Research Plan was posted for public comment on the USPSTF website from April 7, 2022, to May 4, 2022. In response to public comments, the U.S. Preventive Services Task Force made a few minor additions and wording changes to improve clarity, including revisions to the scope of the review to include iron deficiency and iron deficiency anemia during pregnancy. The Contextual Questions were expanded to address the effect of race-based diagnostic cut-offs for anemia on management decisions and health outcomes, in addition to addressing how practices for diagnosis or decisions for supplementation may differ in certain populations.

Several important issues were noted in the comments but did not result in changes to the Research Plan because they were already included or were outside the scope of the proposed work. Comments included suggestions to report ferritin and other maternal hematologic indices, which are already included as maternal intermediate outcomes in both the supplementation and screening Analytic Frameworks. Commenters also suggested considering health outcomes for children older than age 1 year. The rationale for not including infant outcomes beyond the first year of life include lack of evidence supporting associations between maternal iron status and infant outcomes beyond the first year of life to inform decision making. Commenters also suggested including studies conducted outside the United States. Current criteria specifies inclusion of U.S. primary care–relevant studies, including studies from relevant countries outside the United States, to improve applicability for studies conducted in countries with similar nutritional status as all U.S. populations. Countries where nutritional access and practices differ substantially from U.S. populations may be less generalizable and are not included.